Proteome analyses of cultured astrocytes treated with MK-801 and clozapine: similarities with schizophrenia
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On the basis of impaired glutamatergic transmission and the potential role of astrocytes in schizophrenia, we treated cultured astrocytes with MK-801, an NMDA-receptor antagonist, to investigate whether the resulting proteome changes are similar to those we found in our earlier proteome analysis of schizophrenia human brain tissue as well as to better comprehend the role of astrocytes in the disorder. Indeed, there are similarities. Furthermore, to verify the efficacy of clozapine and its effect over the proteome, we treated MK-801-treated astrocytes with clozapine. Interestingly, clozapine reversed protein changes induced by MK-801. The treatment of cell cultures with neural transmission agonists and antagonists might provide useful insights about psychiatric disorders.
KeywordsProteome Proteomics Astrocytes Biomarkers Mass spectrometry Schizophrenia
We would like to thank Dr. Giuseppina Maccarrone, Dr. Jeeva Varadarajulu, and Dr. Claudia Ditzen for the scientific discussion and advice. We also thank Jacquie Klesing, ELS, for editing assistance with the manuscript. The authors declare no competing interests.
- 12.Martins-de-Souza D, Menezes de Oliveira B, dos Santos Farias A, Horiuchi RS, Crepaldi Domingues C, de Paula E, Marangoni S, Gattaz WF, Dias-Neto E, Camillo Novello J (2007) The use of ASB-14 in combination with CHAPS is the best for solubilization of human brain proteins for two-dimensional gel electrophoresis. Brief Funct Genomic Proteomic 6(1):70–75PubMedCrossRefGoogle Scholar
- 13.Martins-de-Souza D, Gattaz WF, Schmitt A, Maccarrone G, Hunyadi-Gulyás E, Eberlin MN, Souza GH, Marangoni S, Novello JC, Turck CW, Dias-Neto E (2009) Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in schizophrenia. J Psychiatr Res 43(11):978–986PubMedCrossRefGoogle Scholar
- 15.Martins-de-Souza D, Gattaz WF, Schmitt A, Rewerts C, Marangoni S, Novello JC, Maccarrone G, Turck CW, Dias-Neto E (2009) Alterations in oligodendrocyte proteins, calcium homeostasis and new potential markers in schizophrenia anterior temporal lobe are revealed by shotgun proteome analysis. J Neural Transm 116(3):275–289PubMedCrossRefGoogle Scholar
- 18.Martins-de-Souza D, Maccarrone G, Wobrock T et al (2010b) Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers for schizophrenia. J Psychiatr Res. doi: 10.1016/j.jpsychires.2010.04.014
- 24.Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffi n JL et al (2004) Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 9:684–697, 643Google Scholar
- 27.Schmitt A, Koschel J, Zink M, Bauer M, Sommer C, Frank J, Treutlein J, Schulze T, Schneider-Axmann T, Parlapani E, Rietschel M, Falkai P, Henn FA (2010) Gene expression of NMDA receptor subunits in the cerebellum of elderly patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 260(2):101–111PubMedCrossRefGoogle Scholar